This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Understanding of the central neural mechanisms mediating fever and cold defense will be relevant for developing therapeutic approaches to combat life-threatening excessive fevers (as during sepsis, toxemia, meningitis, some cancers) and to the management of the effects of thermal dysregulation that occurs during such clinically significant conditions as the abuse of amphetamine-based drugs, the hot flashes accompanying menopause and prostate surgery or the hypothermia induced during surgical anesthesia. The aims of this project are to elucidate the CNS circuits that regulate body temperature and how they are affected by pyrogens. Recent findings include the identification of distinct projections from the fever-inhibited neurons in the preoptic area to the BAT sympathoexcitatory regions of the dorsomedial hypothalamus and to the raphe pallidus, the demonstration that the principal effect of neuronal activation in the paraventricular hypothalamic nucleus is an inhibition of BAT thermogenesis and the elucidation of a prominent disinhibitory role for spinal serotonin release in the cooling-evoked increase in BAT thermogenesis and energy expenditure.